Proinflammatory state promotes red blood cell alloimmunization in pediatric patients with sickle cell disease

We examined risk factors for red blood cell (RBC) alloimmunization in pediatric patients with sickle cell disease, focusing on the recipients’ inflammatory state at the time of transfusion and anti-inflammatory role of hydroxyurea (HU). Among 471 participants, 55 (11.70%) participants were alloimmunized and formed 59 alloantibodies and 17 autoantibodies with an alloimmunization rate of 0.36 alloantibodies per 100 units. Analysis of 27 participants in whom alloantibodies were formed with specificities showed 23.8% (30/126) of units transfused during a proinflammatory event resulting in alloantibody formation compared with 2.8% (27/952) of units transfused at steady state. Therefore, transfusion during proinflammatory events increased the risk for alloimmunization (odds ratio [OR], 4.22; 95% confidence interval [CI], 1.64-10.85; P = .003). Further analysis of all the 471 participants showed that alloimmunization of patients who received episodic transfusion, mostly during proinflammatory events, was not reduced with HU therapy (OR, 6.52; 95% CI, 0.85-49.77; P = .071), HU therapy duration (OR, 1.13; 95% CI, 0.997-1.28; P = .056), or HU dose (OR, 1.06; 95% CI, 0.96-1.16; P = .242). The analysis also identified high transfusion burden (OR, 1.02; 95% CI, 1.003-1.04; P = .020) and hemoglobin S (HbSS) and HbSβ(0)–thalassemia genotypes (OR, 11.22, 95% CI, 1.51-83.38; P = .018) as additional risk factors for alloimmunization. In conclusion, the inflammatory state of transfusion recipients affects the risk of RBC alloimmunization, which is not modified by HU therapy. Judicious use of transfusion during proinflammatory events is critical for preventing alloimmunization.